The present invention relates to a novel enterosoluble capsule for containing a medicament or, more particularly, to an enterosoluble capsule for containing a medicament shaped with a novel enterosoluble cellulose derivative as the base material.
An enterosoluble capsule used for oral administration of a medicament contained therein is required to be stable and undissolved in the stomach but readily dissolved when it arrives at the intestinal canals to release the medicament contained therein. In other words, the solubility of the capsule material depends on the condition of acidity or alkalinity, being insoluble in the acidic condition in the stomach but soluble in the neutral or alkaline condition in the intestinal canals. Enterosoluble capsules having such a solubility performance are conventionally made of gelatine followed by treatment with formalin to modify the solublility or followed by coating with an enterosoluble polymeric material.
One of the problems in such a gelatine-based enterosoluble capsule is the complicacy of the manufacturing process since shaping of a capsule with gelatine must be followed by the formalin treatment or by the coating procedure. Moreover, very delicate control of the process conditions is required in the formalin treatment to impart adequate enterosolubility since a gelatine capsule insufficiently treated with formalin is partly dissolved in the stomach while a gelatine capsule excessively formalin-treated becomes insoluble even in the intestinal canal.
Coating with an enterosoluble polymeric material is also not free from problems of incomplete adhesive bonding between the gelatine surface and the coating film or denaturation of the coating film by the influence of the moisture contained in the gelatine resulting in inferior enterosolubility performance.
On the other hand, there have been proposed enterosoluble capsules shaped with an inherently enterosoluble polymeric material as the base, i.e. a polymeric material which itself is insoluble in the gastric juice but soluble in the intestinal juice. Known examples of such an enterosoluble polymeric material include copolymers of aliphatically unsaturated carboxylic acids such as copolymers of methacrylic acid and methyl methacrylate and certain kinds of cellulose derivatives such as cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, methylcellulose phthalate, cellulose acetate succinate and the like.
In the shaped articles, e.g. capsules, made of the above mentioned copolymers of aliphatically unsaturated carboxylic acids, hydroxypropyl methylcellulose phthalate or methylcellulose phthalate, it is necessary to formulate a considerable amount of a plasticizer in order to improve the hardness and brittleness of the articles so that disadvantages are sometimes unavoidable by the bleeding of the plasticizer on to the surface of the shaped article which may adversely influence the effective ingredient of the medicament contained in the capsule.
Further, cellulose acetate phthalate, cellulose acetate succinate and the like shaped into a capsule are subject to a very undesirable phenomenon that they are hydrolyzed by the influence of the atmospheric moisture in the lapse of time during storage to liberate acid decomposition products such as acetic acid, phthalic acid and succinic acid resulting in gradual decrease of the solubility in the intestinal juice.